Preclinical Safety Assessment and Serum Lipid Profiles of Wister Rats Following Acute and Subchronic Exposure to Water-Soluble Curcuminoid-Rich Extracts

The present study aimed to establish water-soluble curcuminoid-rich extracts and assess their acute and subchronic toxicities, following the OECD guidelines. Water-soluble curcuminoid-rich extracts, namely, CRE-Ter [ternary complex of curcuminoid-rich extract (CRE), hydroxypropyl-β-cyclodextrin, and polyvinylpyrrolidone K30] and CRE-SD (CRE in a solid dispersion form with polyvinylpyrrolidone K30) were produced via green technology, and their curcuminoid content was subsequently quantified using a high-performance liquid chromatographic (HPLC) method. CRE-Ter and CRE-SD contained 17.8% (w/w) total curcuminoids (12.7% (w/w) of curcumin, 3.2% (w/w) of demethoxycurcumin, and 1.9% (w/w) of bisdemethoxycurcumin) and 7.5% (w/w) total curcuminoids (5.2% (w/w) of curcumin, 1.4% (w/w) of demethoxycurcumin, and 0.9% (w/w) of bisdemethoxycurcumin), respectively. The acute and subchronic toxicities of the extracts were investigated in both male and female rats. The limit test of acute toxicity revealed that the oral LD₅₀ of both CRE-Ter and CRE-SD was found to be greater than 2000 mg/kg, with no signs of acute toxicity or mortality during a single dose treatment of 2000 mg/kg. Similarly, regular oral administration of 0, 10, 30, and 300 mg/kg/day of CRE-Ter or CRE-SD for 90 days did not induce any significant toxicological effects on the clinical signs, body weights, food consumption, or water intake of both male and female rats. Moreover, no adverse effects were noted on the hematological or serum biochemical parameters. The gross appearance and histopathological analysis of the major visceral organs in treated groups were comparable to those of the control group. Interestingly, both CRE-Ter and CRE-SD significantly decreased the levels of lipid profiles and fasting blood glucose. These results clearly highlight the excellent safety profiles of CRE-Ter and CRE-SD when administered orally, paving the way for future drug development.